Stereospecific carbon-carbon bond formation by the reaction of a chiral episelenonium ion with aromatic compounds

Article abstract of DOI:10.1016/j.tetlet.2004.06.042

The stereospecific exchange of a hydroxyl group of chiral alcohols bearing a pyridylseleno group on the adjacent carbon atom with aromatic compounds occurred smoothly in the presence of Lewis acid.

Full text of DOI:10.1016/j.tetlet.2004.06.042

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6137–6139
Stereospecific carbon–carbon bond formation by the reaction
of a chiral episelenonium ion with aromatic compounds
Kazuki Okamoto,a Yoshiaki Nishibayashi,a Sakae Uemuraa and Akio Toshimitsub,*
aDepartment of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University,
Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
bInternational Innovation Center, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Received 30 April 2004; revised 9 June 2004; accepted 11 June 2004
Available online 2 July 2004
Abstract—The stereospecific exchange of a hydroxyl group of chiral alcohols bearing a pyridylseleno group on the adjacent carbon
atom with aromatic compounds occurred smoothly in the presence of Lewis acid.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Organic reactions via three-membered episelenonium
OH
Nu
ion intermediate have been widely used in organic syn-
theses.1 Most of the examples have been concerned with
the reactions of an episelenonium ion intermediate with
oxygen- and nitrogen-centered nucleophiles2 and much
less attention has been paid to the reaction with carbon-
centered nucleophiles.
Se
: Nu
Lewis acid
Se
H
H
Ph
Ph
: Nu
H
1a
Ph
+
Se
Recently we have succeeded in the stereospecific car-
bon–carbon bond formation by the reactions of a chiral
episelenonium ion (an episelenonium ion bearing a chi-
ral carbon in the three-membered ring) with carbon-
centered nucleophiles such as alkenyl silyl ethers,
trimethylsilyl cyanide, and allyltrimethylsilane by the
Scheme 1. Reaction of a chiral alcohol bearing a TTBPSe groupon the
adjacent carbon atom (1a) with carbon-centered nucleophile (:Nu) in
the presence of Lewis acid.
use of
a 2,4,6-tri-tert-butylphenylseleno (TTBPSe)
group,3 the role of tert-butyl groups being the steric
protection of the selenium atom to prevent both the
racemization of the chiral carbon atom and the attack of
carbon-centered nucleophiles on the selenium atom
(Scheme 1).4 In order to find a new aspect of this
chemistry, we have now investigated the reaction of a
chiral episelenonium ion with aromatic compounds such
as carbon nucleophiles. As a result, we found that (1) a
carbon–carbon bond forming reaction proceeds even
without the steric protection of the selenium atom, and
(2) when a 2-pyridyl group is employed as the sub-
stituent on the selenium atom, stereospecificity of the
reaction depends greatly on the reactivity of aromatic
compounds.
By the reaction of a chiral alcohol bearing a phenyl-
seleno groupon the adjacent carbon atom ( 1c) (>99%
ee) with anisole in the presence of trifluoroborane–di-
ethyl ether (Scheme 2), substitution of a hydroxyl group
by the aromatic carbon proceeded to afford 2c in high
yield. It should be noted that the substitution occurred
selectively at the para-position of anisole. Enantiomeric
excess of 2c, on the other hand, was found to be only
2%. These results indicate that the aromatic carbon
attacks selectively on the carbon atom of the episele-
nonium ion bearing a phenyl group on the selenium
atom, while the chiral carbon in the episelenonium ion
racemizes almost completely during the reaction.
Keywords: Stereospecific reaction.
* Corresponding author. Tel.: +81-7575-39174; fax: +81-7575-39145;
e-mail: akiot@iic.kyoto-u.ac.jp
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.06.042

6138
K. Okamoto et al. / Tetrahedron Letters 45 (2004) 6137–6139
Table 1. Reaction of a chiral alcohol bearing a 2-pyridylseleno group
OMe
OMe
on the adjacent carbon atom (1b) with a variety of aromatic com-
pounds (10 equiv) in the presence of BF3ÆOEt2 (10 equiv)a
H
OH
BF3·OEt2
Ph
Run
Aromatic
compound
Substituted
product 2
Yield
ee of
+
SeAr
CH2Cl2, 25 ° C
25 °C, 2 h
H
Se
of 2 (%)b 2 (%)c
SeAr
Ph
H
Ar
Ph
1a; Ar = TTBP
2a; Ar = TTBP
2b; Ar = Py
85% yield; 98% ee
89% yield; 95% ee
1b; Ar = 2-pyridyl (Py)
1c; Ar = phenyl
2d
1
51
99
2c; Ar = phenyl 71% yield; 2% ee
SePy
H
Ph
Scheme 2. Reactions of chiral alcohols bearing various arylseleno
groups on the adjacent carbon atom (1) with anisole (10 equiv) in the
presence of BF3ÆOEt2 (10 equiv).5
Fe
2e
SePy
2
3
4
5
27
66
87
66
99
96
92
86
Fe
H
Ph
When a chiral alcohol bearing a 2-pyridylseleno group
(1b) (>99% ee) was used as substrate, the corresponding
substituted product (2b) was obtained in 89% yield. The
enantiomeric excess of 2b was found to be 95%. It has
already been reported that the racemization of the chiral
carbon in the episelenonium ion was retarded greatly by
changing the substituent on the selenium atom from
phenyl to 2-pyridyl group.6 As expected, the reaction of
a chiral alcohol bearing a TTBPSe groupon the adja-
cent carbon atom (1a) with anisole afforded the corres-
ponding substituted product (2a) in 85% yield with
98% ee.
2f
SePy
O
S
O
S
H
Ph
2g
SePy
H
Ph
OMe
OMe
OMe
2h
MeO
MeO
SePy
H
Ph
In order to know the reason for the slight loss of optical
purity during the reaction of a chiral episelenonium ion
bearing a 2-pyridyl group with anisole described above,
the reaction of 1b with a variety of aromatic compounds
was investigated in detail. Typical results are shown in
Table 1. The reactions of 1b with azulene and ferrocene
proceeded smoothly to give the corresponding substi-
tuted products (2d and 2e) in good yields without the
loss of optical purity (runs 1 and 2). By the reaction of
1b with heterocyclic aromatic compounds such as
2-methylfuran and 2-methylthiophene, the correspond-
ing substituted products (2f and 2g7) were obtained in
high yields with a slight loss of optical purity (runs 3 and
4). The reactions of 1b with 1,4-dimethoxybenzene and
1,3,5-trimethoxybenzene were also accompanied by a
partial racemization (runs 5 and 6). However, the reac-
tions of 1b with less reactive aromatic compounds such
as toluene, p-xylene, and 1,3,5-trimethylbenzene affor-
ded the corresponding substituted products (2j–l) in
moderate yields with low enantiomeric purity (runs 7–9).
Thus, enantiomeric purity of the chiral carbon atom of 2
was found to depend much on the electronic nature of
aromatic compounds employed. It should be noted
here that, in the reaction of 1b with 1,3,5-trimethyl-
benzene, the products were found to be a mixture
of regioisomers (2l and 2l0), the ratio of isomers being
2:1.
OMe
MeO
2i
OMe
6
66
96
MeO
OMe
SePy
H
Ph
2j
7
8
9
35
49
24
SePy
H
Ph
2k
8
SePy
H
Ph
2l
SePy
57d
13
H
Ph
a Reactions conditions: 1b (0.30 mmol), BF3ÆOEt2 (3.00 mmol), aro-
matic compound (3.00 mmol), dichloromethane (15 mL) at 25 ꢁC for
2 h under nitrogen atmosphere.
b Isolated yield.
c Determined by HPLC analysis using chiral columns, Chiralcel OJ or
OD.
d Other regioisomer (2l0) was formed. The isomer ratio of 2l and 2l0 was
2:1.
PySe
H
tion due to the double inversion during the formation
and reaction of the episelenonium ion.3
Ph
2l'
To our knowledge, this is the first example of the stereo-
selective intermolecular reaction of a chiral episele-
nonium ion with aromatic compounds, although a
The stereochemistry of the chiral carbon atoms of the
products is considered to be the retention of configura-

K. Okamoto et al. / Tetrahedron Letters 45 (2004) 6137–6139
6139
rini, A. Chem. Eur. J. 2002, 8, 1118; (m) Uehlin, L.;
Fragale, G.; Wirth, T. Chem. Eur. J. 2002, 8, 1125; (n)
Tiecco, M.; Testaferri, L.; Santi, C.; Tomassini, C.; Marini,
F.; Bagnoli, L.; Temperini, A. Angew. Chem., Int. Ed. 2003,
42, 3131.
stereoselective intramolecular cyclization of the ion with
8
benzene derivatives has been reported by Deziel et al.
ꢀ
The reaction described here may provide a new proce-
dure for chiral compounds, which can be used for the
preparation of chiral hydrocarbons bearing an aryl
groupat the asymmetric carbon atom with the predict-
able configuration. Moreover, our findings should pro-
vide a new opportunity to elucidate the mechanism of
the racemization of the chiral carbon in episelenonium
ion intermediates and to developa new methodology for
the synthetically important carbon–carbon bond form-
ing reactions. Further work is currently in progress
aiming at the elucidation of the reaction mechanism and
broading the scope of asymmetric synthesis.
3. (a) Toshimitsu, A.; Nakano, K.; Mukai, T.; Tamao, K.
J. Am. Chem. Soc. 1996, 118, 2756; (b) Toshimitsu, A.;
Terada, M.; Tamao, K. Chem. Lett. 1997, 733.
4. (a) Clive, D. L. J.; Chittattu, G.; Wong, C. K. J. Chem.
Soc., Chem. Commun. 1978, 0, 441; (b) Rouessac, F.;
Zamarlik, H. Tetrahedron Lett. 1981, 22, 2643; (c) Ley,
S. V.; Lygo, B.; Moliness, H.; Morton, J. A. J. Chem. Soc.,
Chem. Commun. 1982, 1251; (d) Alexander, R. P.; Paterson,
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5. The enantiomeric excess of products slightly decreased
when less than 10 equiv of Lewis acid was used.
6. Toshimistu, A.; Ito, M.; Uemura, S. J. Chem. Soc., Chem.
Commun. 1989, 530.
7. A typical procedure is as follows. To a solution of (R)-2-
pyridylseleno-1-phenylethanol (1b; 84 mg, 0.30 mmol;
>99% ee) and thiophene (295 mg, 3.00 mmol) in dichloro-
methane (15 mL) was added trifluoroborane–diethyl ether
complex (0.90 mL, 3.00 mmol) at 25 ꢁC under nitrogen
atmosphere, and then the resulting mixture was stirred at
25 ꢁC for 2 h. The mixture was then quenched with water
(10 mL) and extracted with dichloromethane (20 mL · 3).
The combined organic layer was washed with brine, dried
over anhydrous MgSO4, and then concentrated under
reduced pressure. Purification of the residue by column
chromatography gave 2g as a pale yellow oil (94 mg,
0.26 mmol; 87% yield; 92% ee). Selected spectroscopic data
for 2g: 1H NMR (300 MHz, CDCl3) d 2.40 (3H, s), 3.87
(2H, dd, J ¼ 7:8, 2.1 Hz), 4.52 (1H, dd, J ¼ 7:8 Hz), 6.57
(1H, d, J ¼ 3:0), 6.69 (1H, d, J ¼ 3:0), 7.03 (1H, t, J ¼ 6:0),
7.21–7.31 (7H, m), 7.41 (1H, t, J ¼ 7:5), 8.46 (1H, d,
J ¼ 4:5); 13C NMR (75 MHz, CDCl3) d 15.3, 32.6, 47.4,
120.3, 124.3, 124.6, 125.7, 127.0, 127.7, 128.5, 136.2, 138.5,
143.6, 145.4, 149.6, 155.0 (Found: C, 60.5; H, 4.8; N, 3.9.
Acknowledgements
This work was supported by Grant-in Aid for Scientific
Research (No. 14044047) from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Japan.
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